Adrenoleukodystrophy (ALD) is a rare, inherited metabolic disorder. In this disorder, the fatty covering (myelin sheath) of nerve fibres in the brain is lost, and the adrenal gland degenerates, usually leading to progressive neurological disability and death. A good portrayal of the effects of ALD on both the victim and family is the film “Lorenzo’s Oil”. It accurately describes the deterioration of a young boy with the disorder and resultant problems. The film does intimate that a cure (Lorenzo’s Oil) was found. Unfortunately this is not the case for those already with symptoms, although the oil is now a recognised and hopefully preventative treatment for all boys under 6 with the gene who are not presenting symptoms. It is now also being tested as a preventative treatment for men with adrenomyeloneuropathy (AMN) and females with symptoms.

There are four known prognoses for people with the adrenoleukodystrophy gene:

 

Neonatal ALD in which the disorder will progress very quickly until death and can affect males and females.

Childhood X-linked ALD. This is thought to be the most common. It is known as an x-linked disorder as the abnormal gene is located on the x-chromosome; it is carried by females (who have two x-chromosomes and so the healthy one effectively cancels out the other) and passed on to males (who have only one x-chromosome). It will usually present in boys aged between 4 and 10 starting with abnormal or uncharacteristic behaviour, coordination problems and a decline in school performance. This will normally progress to deterioration in all functions including speech, hearing, sight, swallowing, mobility and dementia usually within months of initial symptoms. The affected child will eventually be completely dependent and the family will need full support and assistance from the health and social services. Death will normally ensue within one to ten years. In some cases the disorder appears to arrest and the subject will live into adulthood.

Adult X-linked ALD. This is similar to childhood x-linked ALD but affects mature males from 40 onwards. There are more and more cases of this arising and it is now thought that it is more common and has been previously misdiagnosed.

Adrenomyeloneuropathy (AMN). This normally begins between the ages of 21-35 and is a milder form of the disorder affecting mainly the spinal cord and nerves. Symptoms are usually progressive stiffness, weakness or paralysis of the lower limbs, and ataxia (coordination problems). Although this is normally a more physically symptomatic form, it can result in deterioration of brain function.

ALD is thought to be caused by the body’s inability to digest very long chain fatty acids (VLCFAs). These build up in the brain and destroy the myelin sheath. The peroxisome¹ is responsible for this; to understand more please see www.peroxisome.org. A good analogy is that of an electric cable in which the flex is cracked and worn thus exposing the wiring within. The connection between the body and brain is there, but the messages to tell the body what to do cannot be transmitted as the myelin is depleted, and it is this substance that carries the impulses. For example, in a child affected by x-linked childhood ALD, there is nothing physically wrong with their eyesight but the message from the eye to the brain to determine what is being seen cannot get through.

All forms of ALD will most likely also have adrenal failure, which must be treated with replacement steroids and monitored carefully. However this is not always the case, and conversely some carriers of the adrenoleukodystrophy gene will have adrenal failure but no neurological problems.

Female carriers (heterozygotes) may experience mild symptoms in later years including progressive stiffness, weakness or paralysis of the lower limbs, ataxia, excessive muscle tone, mild peripheral neuropathy (possible numbness, weakness, burning pain (especially at night), and loss of reflexes) and urinary problems. Some females may go on to suffer more serious symptoms similar to adrenomyeloneuropathy.

Treatment for those with advanced adrenoleukodystrophy and adrenomyeloneuropathy is largely based on management of symptoms. At present there is no cure.

Detection of the disorder is extremely difficult unless the patient prior presents with adrenal failure. Any child with adrenal failure should be tested for the adrenoleukodystrophy gene immediately. If the gene is present then all family members must be tested. There is a 50% chance of passing on the gene and although women do not have such serious symptoms, the chance of them again passing the gene on to their own children is not a risk that should be taken lightly. Any females carrying the gene should be offered pre-implantation genetic diagnosis when starting a family of their own should they wish it. Although males cannot pass the gene to their sons, they can pass it to their daughters and this fact should not be ignored when doing genetic testing.

Once the disorder is diagnosed, the patient should be offered MRI and MRS scans every six months. The MRI scan detects early damage to the white matter of the brain and the MRS scan is a new method of measuring the thickness of the myelin sheath. The patient should also be checked regularly for adrenal failure usually presented by increased pigmentation changes (yellowing of the skin) and/or excessive tiredness. It is now also good practice for patients under six years old to be prescribed Lorenzo’s Oil taken in conjunction with a very low fat diet. Go to  http://www.aldlife.org/lorenzos_low_fat_diet.php for more information. Research, although not conclusive, is showing that this may well slow if not stop the advance of myelin deterioration. In any case it is not a treatment that should be denied. If myelin deterioration is detected by scan then the only available treatment is bone marrow transplant. It is essential that upon diagnosis a suitable bone marrow match is found for the patient as soon as possible. http://www.aldlife.org/bone_marrow_transplant.php